Our developing understanding of the virology of SARS-CoV-2 suggests the biologic plausibility of heparin as an antiviral. Theoretically, heparin may bind the SARS-CoV-2 spike protein and function as a competitive inhibitor for viral entry, thus decreasing infectivity. Interestingly, shorter-length heparins, comparable to those found in therapeutic low-molecular weight heparin, did not appreciably bind the spike protein (17), suggesting that low-molecular weight formulations may be less likely to have direct antiviral activity through competitive spike protein binding. If clinical trials demonstrate benefit of unfractionated heparin therapy, its effect could be partially due to this theoretical antiviral activity, rather than solely due to its anticoagulant properties (38). As such, clinical trials with heparin should evaluate disease course and time to clearance of infection, as these outcomes would support direct antiviral activity.